Metagenomics and the Human Virome in Asymptomatic Individuals

Rascovan, Nicolás; Duraisamy, Raja; Desnues, Christelle

doi:10.1146/annurev-micro-102215-095431

Cited by 116 publications

(93 citation statements)

References 116 publications

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“…In a typical human with 10 12 nucleated cells, it is estimated that there are 10 15 virions and 10 13 bacteria (1, 2). In the past, only the components of the microbiome that could be directly visualized or grown in culture were readily appreciated (3).…”

Section: Introductionmentioning

confidence: 99%

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

et al. 2017

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Background Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings. Objective To explore the plasma virome of persons who inject drugs while characterizing the sensitivity and accuracy of NGMS compared to quantitative clinical standards. Design Longitudinal and cross-sectional studies. Participants Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infected persons enrolled in a clinical trial (NCT01285050) and/or a well-characterized cohort study of persons who have injected drugs. Measurements Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR). Results NGMS generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained >10,000 copies or IU/ml as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1) was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Because of this unexpected finding, using a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs in whom HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses such as HCV RNA and SEN virus D Limitations The medical importance of HHpgV-1infection remains unknown. Conclusions Although NGMS is insensitive to detection of viruses with relatively low plasma nucleic acid concentrations, it may have a broad potential for discovery of new viral infections of potential medical importance like HHpgV-1.

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Section: Introductionmentioning

confidence: 99%

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

et al. 2017

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“…A thorough review has been published recently [9]. Many viruses are present in peripheral blood—in particular, members of the Herpesviridae and Anelloviridae families are identified in the absence of disease.…”

Section: Introductionmentioning

confidence: 99%

“…Metagenomic studies also lead to the identification of novel RNA viruses—for example the identification of two rhabdoviruses [13]. Other viral sequences in the blood of healthy individuals are related to members of the Picornaviridae, Poxviridae, Flaviviridae, and Phycodnaviridae families (reviewed in [9]). Finally, a number of viruses, prominently retroviruses, are integrated in the human genome as provirus, while others may integrate occasionally or accidentally [14].…”

Section: Introductionmentioning

confidence: 99%

The blood DNA virome in 8,000 humans

Moustafa¹,

Xie²,

Kirkness³

et al. 2017

PLoS Pathog

272

258

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The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.

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“…Annelloviruses are the most prevalent family [4], and metagenomics studies have identified a great degree of genetic diversity within this group [5, 6], including TTV which are separated into 39 genotypes and infect the majority of humans without any presentation of symptoms. Other viruses found in the blood of the healthy and asymptomatic populations are members of the Picornaviridae, Poxviridae, Flaviviridae, rhabdoviruses and Phycodnaviridae families [7, 8]. Recently, in a study using NGS to analyze the blood of 8,240 individuals without any symptoms of infectious diseases [4], it was reported that 94 viral species were identified, of which 19 were found in 42% of participants.…”

Section: Metagenomics In Human Bloodmentioning

confidence: 99%

Viral Metagenomics of Blood Donors and Blood-Derived Products Using Next-Generation Sequencing

Waldvogel-Abramowski

Taleb

Alessandrini

et al. 2019

Transfus Med Hemother

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Transfusion-transmitted infections remain a permanent threat in medicine. It keeps the burden of the past, marked by serious infections transmitted by transfusion, and is constantly threatened by emerging viruses. The global rise of immunosuppression among patients undergoing frequent transfusions exacerbates this problem. Over the past decade, criteria for donor selection have become increasingly more stringent. Although routine nucleic acid testing (NAT) for virus-specific detection has become more sensitive, these safety measures are only valuable for a limited number of select viruses. The scientific approach to this is however changing, with the goal of trying to identify infectious agents in donor units as early as possible to mitigate the risk of a clinically relevant infection. To this end, and in addition to an epidemiological surveillance of the general population, researchers are adopting new methods to discover emerging infectious agents, while simultaneously screening for an extended number of viruses in donors. Next-generation sequencing (NGS) offers the opportunity to explore the entire viral landscape in blood donors, the so-called metagenomics, to investigate severe transfusion reactions of unknown etiology. In the not too distant future, one could imagine this platform being used for routine testing of donated blood products.

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Metagenomics and the Human Virome in Asymptomatic Individuals

Cited by 116 publications

References 116 publications

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

The blood DNA virome in 8,000 humans

Viral Metagenomics of Blood Donors and Blood-Derived Products Using Next-Generation Sequencing

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